Highly Reactive Isolevuglandins Promote Atrial Fibrillation Caused by Hypertension.

Citation
Prinsen, J. K., et al. “Highly Reactive Isolevuglandins Promote Atrial Fibrillation Caused By Hypertension.”. Jacc. Basic To Translational Science, pp. 602-615.
Center Vanderbilt University
Author Joseph K Prinsen, Prince J Kannankeril, Tatiana N Sidorova, Liudmila Yermalitskaya V, Olivier Boutaud, Irene Zagol-Ikapitte, Joey Barnett V, Matthew B Murphy, Tuerdi Subati, Joshua M Stark, Isis L Christopher, Scott R Jafarian-Kerman, Mohamed A Saleh, Allison E Norlander, Roxana Loperena, James B Atkinson, Agnes B Fogo, James M Luther, Venkataraman Amarnath, Sean S Davies, Annet Kirabo, Meena S Madhur, David G Harrison, Katherine T Murray
Keywords 2-HOBA, 2-hydroxylbenzylamine, 4-HOBA, 4-hydroxylbenzylamine, AF, atrial fibrillation, ANP, atrial natriuretic peptide, B-type natriuretic peptide, BNP, B-type natriuretic peptide, BP, blood pressure, ECG, electrocardiogram, G/R, green/red ratio, IsoLG, isolevuglandin, PAO, preamyloid oligomer, PBS, phosphate-buffered saline, ROS, reactive oxygen species, ang II, angiotensin II, atrial fibrillation, atrial natriuretic peptide, hypertension, isolevuglandins, oxidative stress, preamyloid oligomers
Abstract

Oxidative damage is implicated in atrial fibrillation (AF), but antioxidants are ineffective therapeutically. The authors tested the hypothesis that highly reactive lipid dicarbonyl metabolites, or isolevuglandins (IsoLGs), are principal drivers of AF during hypertension. In a hypertensive murine model and stretched atriomyocytes, the dicarbonyl scavenger 2-hydroxybenzylamine (2-HOBA) prevented IsoLG adducts and preamyloid oligomers (PAOs), and AF susceptibility, whereas the ineffective analog 4-hydroxybenzylamine (4-HOBA) had minimal effect. Natriuretic peptides generated cytotoxic oligomers, a process accelerated by IsoLGs, contributing to atrial PAO formation. These findings support the concept of pre-emptively scavenging reactive downstream oxidative stress mediators as a potential therapeutic approach to prevent AF.

Year of Publication
2020
Journal
JACC. Basic to translational science
Volume
5
Issue
6
Number of Pages
602-615
Date Published
06/2020
ISSN Number
2452-302X
DOI
10.1016/j.jacbts.2020.04.004
Alternate Journal
JACC Basic Transl Sci
PMID
32613146
PMCID
PMC7315188